search
Back to results

Study of BN301, an Anti-CD74 Antibody Drug Conjugate, in Patients With Advanced B-Cell Malignancies

Primary Purpose

B-cell Lymphoma, Non Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
BN301
Sponsored by
BioNova Pharmaceuticals (Shanghai) LTD.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B-cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Have been fully informed about the study and have voluntarily signed the ICF; Age ≥ 18 years; Histologically confirmed as B-cell NHL (pathology report), including DLBCL, FL, MZL, and MCL, etc., and the disease requires further treatment; Have relapsed/refractory disease or intolerance to prior therapy after ≥ 2 prior lines of therapy including anti-CD20 antibody-containing chemotherapy regimens (e.g., R-CHOP, etc.) (see Section 3.1 for specific definitions); At least 1 radiographically measurable lesion (≥ 1 lymph node lesion with longest diameter of > 1.5 cm, and/or extranodal lesion with longest diameter of >1.0 cm, as assessed by computed tomography [CT]), and no prior radiotherapy on the lesion (evidence of unequivocal progression is required if the lesion has received prior radiotherapy); ECOG score 0-2; Adequate hematological status (supportive care such as growth factor, platelet transfusion or blood transfusion or correction with drugs are not allowed within 5 days prior to screening): Absolute neutrophil count (ANC) ≥ 1.5 × 109/L Platelets ≥ 75 × 109/L Hemoglobin ≥ 9 g/dL Note: In Phase 2, if the investigator believes that the above values below the lower limit of the protocol are due to bone marrow involvement by lymphoma, the patient could be enrolled after consultation between investigator and the Sponsor and obtaining written consent from the Sponsor; Adequate hepatic, renal, and cardiac functions, defined as: Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 2.5 × upper limit of normal (ULN); Total bilirubin ≤ 1.5 × ULN, total bilirubin ≤ 3 × ULN for patients with Gilbert's disease; Creatinine clearance ≥ 50 mL/min as estimated by the Cockcroft-Gault f formula (if < 50 mL/min, e.g., creatinine ≤ 130 μmol/L is also allowed); Left ventricular ejection fraction ≥ 45%; Note: In Phase 2, the criteria for ALT or AST may be relaxed to ≤ 5 × ULN if the investigator assesses that the increase in ALT or AST is due to liver invasion by lymphoma; Male or female patients of childbearing potential must agree to use effective methods of contraception, such as double barrier methods of contraception, condoms, oral or injectable contraceptives, intrauterine devices, etc., during the study and within 90 days after the last dose of study drug. Postmenopausal women (> 45 years of age and menopause for more than 1 year) and surgically sterilized women are not subject to this condition. Exclusion Criteria: Chronic lymphocytic leukemia and T-cell malignancies; Primary central nervous system lymphoma or lymphoma involving the central nervous system; Known history of hepatitis B (HBsAg positive) or hepatitis C (HCV antibody positive). Subjects with occult or pre-hepatitis B infection (defined as HBcAb positive, HBsAg negative) could be enrolled if HBV DNA test result is negative, and subjects with serologically positive HCV antibody, such as negative HCV RNA test result, could also be enrolled; Known human immunodeficiency virus (HIV) infection; Concomitant clinically significant active infections requiring systemic treatment, including but not limited to chronic kidney infection, chronic chest infection with bronchiectasis and tuberculosis, etc.; Expected survival of no more than 24 weeks as judged by the investigator; Previous solid organ transplant; autologous hematopoietic stem cell transplant, allogeneic hematopoietic stem cell transplant, or chimeric antigen receptor T-cell (CAR-T) therapy within 60 days prior to enrollment, or had the following conditions: Active graft versus host disease (GVHD); Cytopenia due to unrecovered hematopoiesis after transplantation; Anti-cytokine therapy (e.g., tocilizumab, glucocorticoids) is still required due to CAR-T cell treatment toxicity, or neurological toxicity is > Grade 1 after CAR-T cell therapy; Continuous use of immunosuppressive therapy; Pregnant (positive pregnancy test at screening) or lactating female patients; QTcF > 450 msec in male patients or QTcF > 470 msec in female patients or other significant ECG abnormalities as judged by the investigator; Toxicities due to prior anti-lymphoma therapy have not stabilized and have not recovered to ≤ Grade 1 (except for clinically insignificant toxicities such as alopecia, etc.); Other malignancies in the past 5 years, with the exception of radically treated basal cell carcinoma of skin, breast cancer in situ and cervix carcinoma in situ; The time from prior systemic anti-tumor therapy or investigational therapy to the start of the planned study treatment is less than 4 weeks or 5 half-lives (whichever is shorter); History of acute myocardial infarction, unstable angina pectoris, stroke, intracranial hemorrhage or transient ischemic attack within 6 months prior to enrollment; New York Heart Association (NYHA) Grade 3 and 4 congestive heart failure; History of deep vein thrombosis or pulmonary embolism within 6 months prior to enrollment (Phase 1 dose escalation part only); Grade ≥ 2 sensory or motor neuropathy; Known severe chronic obstructive pulmonary disease or asthma, defined as forced expiratory volume in one second (FEV1) < 60% of expected value; Prior therapies targeting CD74; Insufficient compliance of patients participating in this clinical study as judged by the investigator; Any other disease, metabolic abnormality, physical examination abnormality, or clinically significant laboratory abnormality, for which in the investigator's judgment, there is reason to suspect that the patient has a disease or condition that is not suitable for the study drug, or will affect the interpretation of the study results, or place the patient at high risk (e.g., the suitability of patients for inclusion in the study will be determined by the investigator if they have recovered from COVID-19); Live viral vaccination within 28 days prior to the first dose of study drug.

Sites / Locations

  • The first affiliated hospital, Zhejiang Unviersity school of medicineRecruiting
  • The First Affiliated School of Guangxi Medical UniversityRecruiting
  • Shanghai Jiao Tong University School of Medicine, Ruijin HospitalRecruiting
  • The First Affiliated Hospital of Soochow UniversityRecruiting
  • Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyRecruiting
  • Henan Oncology HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

3.5mg/kg

4.2mg/kg

5.0mg/kg

Arm Description

Will be administered by intravenous infusion every 3 weeks on D1

Will be administered by intravenous infusion every 3 weeks on D1

Will be administered by intravenous infusion every 3 weeks on D1

Outcomes

Primary Outcome Measures

Incidence of Treatment-Related Adverse Events as Assessed by CTCAE v4.0.3
Safety and tolerability
Objective Response Rate of participants as assessed by the Lugano 2014 criteria.
Efficacy

Secondary Outcome Measures

Maximum concentration (Cmax)
Cmax of BN301 in plasma of each subject
Time to maximum concentration (Tmax)
Tmax of BN301 in plasma of each subject
Elimination half-life (t1/2)
Elimination half-life (t1/2) of BN301 in plasma of each subject
Area under the plasma concentration-time curve (AUC0-t)
Area under the plasma concentration-time curve (AUC0-t) of BN301 in plasma of each subject
CD74 expression
The analysis of correlation between CD74 expression and BN301 efficacy

Full Information

First Posted
October 26, 2022
Last Updated
March 23, 2023
Sponsor
BioNova Pharmaceuticals (Shanghai) LTD.
search

1. Study Identification

Unique Protocol Identification Number
NCT05611853
Brief Title
Study of BN301, an Anti-CD74 Antibody Drug Conjugate, in Patients With Advanced B-Cell Malignancies
Official Title
A Multicenter Phase 1/2 Clinical Study to Evaluate the Safety and Efficacy of BN301,An Anti-CD74 Antibody Drug Conjugate, in Patients With Advanced B-cell Non-Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 25, 2022 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioNova Pharmaceuticals (Shanghai) LTD.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Phase 1/2 trial to study the safety, pharmacokinetics and preliminary efficacy of BN301 given intravenously every 3 weeks.
Detailed Description
This is a multicenter, open-label Phase 1/2 clinical study to evaluate BN301 administered intravenously in patients with B-cell NHL who have previously failed standard therapy or who are intolerant to standard therapy. This study includes two parts: a Phase 1 dose escalation part and a Phase 2 dose expansion part. In Phase 1 and Phase 2, BN301 will be administered intravenously on Day 1 of every 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent, loss to follow-up, death, or other conditions in which patients are not suitable for study treatment, whichever occurs first. Laboratory tests will be performed weekly in Cycles 1-4 and every 3 weeks from Cycle 5 onwards (see Study Flow Chart). PK sample analysis will be performed on Days 1, 2, and 8 of the first two treatment cycles, Day 1 of the third treatment cycle, and at specified time points at the end of treatment (see Attachment 1). Additional clinical assessments and laboratory tests may be performed at discretion of the investigator as clinically indicated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Lymphoma, Non Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
3.5mg/kg
Arm Type
Experimental
Arm Description
Will be administered by intravenous infusion every 3 weeks on D1
Arm Title
4.2mg/kg
Arm Type
Experimental
Arm Description
Will be administered by intravenous infusion every 3 weeks on D1
Arm Title
5.0mg/kg
Arm Type
Experimental
Arm Description
Will be administered by intravenous infusion every 3 weeks on D1
Intervention Type
Drug
Intervention Name(s)
BN301
Other Intervention Name(s)
STRO-001
Intervention Description
BN301 will be administered intravenously on Day 1 of every 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent, loss to follow-up, death, or other conditions in which patients are not suitable for study treatment, whichever occurs first. Since this is the first time BN301 will be used in Chinese patients, it is planned to enroll 1 subject at the first dose level of 3.5 mg/kg.
Primary Outcome Measure Information:
Title
Incidence of Treatment-Related Adverse Events as Assessed by CTCAE v4.0.3
Description
Safety and tolerability
Time Frame
12 months
Title
Objective Response Rate of participants as assessed by the Lugano 2014 criteria.
Description
Efficacy
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Maximum concentration (Cmax)
Description
Cmax of BN301 in plasma of each subject
Time Frame
12 months
Title
Time to maximum concentration (Tmax)
Description
Tmax of BN301 in plasma of each subject
Time Frame
12 months
Title
Elimination half-life (t1/2)
Description
Elimination half-life (t1/2) of BN301 in plasma of each subject
Time Frame
12 months
Title
Area under the plasma concentration-time curve (AUC0-t)
Description
Area under the plasma concentration-time curve (AUC0-t) of BN301 in plasma of each subject
Time Frame
12 months
Title
CD74 expression
Description
The analysis of correlation between CD74 expression and BN301 efficacy
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Have been fully informed about the study and have voluntarily signed the ICF; Age ≥ 18 years; Histologically confirmed as B-cell NHL (pathology report), including DLBCL, FL, MZL, and MCL, etc., and the disease requires further treatment; Have relapsed/refractory disease or intolerance to prior therapy after ≥ 2 prior lines of therapy including anti-CD20 antibody-containing chemotherapy regimens (e.g., R-CHOP, etc.) (see Section 3.1 for specific definitions); At least 1 radiographically measurable lesion (≥ 1 lymph node lesion with longest diameter of > 1.5 cm, and/or extranodal lesion with longest diameter of >1.0 cm, as assessed by computed tomography [CT]), and no prior radiotherapy on the lesion (evidence of unequivocal progression is required if the lesion has received prior radiotherapy); ECOG score 0-2; Adequate hematological status (supportive care such as growth factor, platelet transfusion or blood transfusion or correction with drugs are not allowed within 5 days prior to screening): Absolute neutrophil count (ANC) ≥ 1.5 × 109/L Platelets ≥ 75 × 109/L Hemoglobin ≥ 9 g/dL Note: In Phase 2, if the investigator believes that the above values below the lower limit of the protocol are due to bone marrow involvement by lymphoma, the patient could be enrolled after consultation between investigator and the Sponsor and obtaining written consent from the Sponsor; Adequate hepatic, renal, and cardiac functions, defined as: Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 2.5 × upper limit of normal (ULN); Total bilirubin ≤ 1.5 × ULN, total bilirubin ≤ 3 × ULN for patients with Gilbert's disease; Creatinine clearance ≥ 50 mL/min as estimated by the Cockcroft-Gault f formula (if < 50 mL/min, e.g., creatinine ≤ 130 μmol/L is also allowed); Left ventricular ejection fraction ≥ 45%; Note: In Phase 2, the criteria for ALT or AST may be relaxed to ≤ 5 × ULN if the investigator assesses that the increase in ALT or AST is due to liver invasion by lymphoma; Male or female patients of childbearing potential must agree to use effective methods of contraception, such as double barrier methods of contraception, condoms, oral or injectable contraceptives, intrauterine devices, etc., during the study and within 90 days after the last dose of study drug. Postmenopausal women (> 45 years of age and menopause for more than 1 year) and surgically sterilized women are not subject to this condition. Exclusion Criteria: Chronic lymphocytic leukemia and T-cell malignancies; Primary central nervous system lymphoma or lymphoma involving the central nervous system; Known history of hepatitis B (HBsAg positive) or hepatitis C (HCV antibody positive). Subjects with occult or pre-hepatitis B infection (defined as HBcAb positive, HBsAg negative) could be enrolled if HBV DNA test result is negative, and subjects with serologically positive HCV antibody, such as negative HCV RNA test result, could also be enrolled; Known human immunodeficiency virus (HIV) infection; Concomitant clinically significant active infections requiring systemic treatment, including but not limited to chronic kidney infection, chronic chest infection with bronchiectasis and tuberculosis, etc.; Expected survival of no more than 24 weeks as judged by the investigator; Previous solid organ transplant; autologous hematopoietic stem cell transplant, allogeneic hematopoietic stem cell transplant, or chimeric antigen receptor T-cell (CAR-T) therapy within 60 days prior to enrollment, or had the following conditions: Active graft versus host disease (GVHD); Cytopenia due to unrecovered hematopoiesis after transplantation; Anti-cytokine therapy (e.g., tocilizumab, glucocorticoids) is still required due to CAR-T cell treatment toxicity, or neurological toxicity is > Grade 1 after CAR-T cell therapy; Continuous use of immunosuppressive therapy; Pregnant (positive pregnancy test at screening) or lactating female patients; QTcF > 450 msec in male patients or QTcF > 470 msec in female patients or other significant ECG abnormalities as judged by the investigator; Toxicities due to prior anti-lymphoma therapy have not stabilized and have not recovered to ≤ Grade 1 (except for clinically insignificant toxicities such as alopecia, etc.); Other malignancies in the past 5 years, with the exception of radically treated basal cell carcinoma of skin, breast cancer in situ and cervix carcinoma in situ; The time from prior systemic anti-tumor therapy or investigational therapy to the start of the planned study treatment is less than 4 weeks or 5 half-lives (whichever is shorter); History of acute myocardial infarction, unstable angina pectoris, stroke, intracranial hemorrhage or transient ischemic attack within 6 months prior to enrollment; New York Heart Association (NYHA) Grade 3 and 4 congestive heart failure; History of deep vein thrombosis or pulmonary embolism within 6 months prior to enrollment (Phase 1 dose escalation part only); Grade ≥ 2 sensory or motor neuropathy; Known severe chronic obstructive pulmonary disease or asthma, defined as forced expiratory volume in one second (FEV1) < 60% of expected value; Prior therapies targeting CD74; Insufficient compliance of patients participating in this clinical study as judged by the investigator; Any other disease, metabolic abnormality, physical examination abnormality, or clinically significant laboratory abnormality, for which in the investigator's judgment, there is reason to suspect that the patient has a disease or condition that is not suitable for the study drug, or will affect the interpretation of the study results, or place the patient at high risk (e.g., the suitability of patients for inclusion in the study will be determined by the investigator if they have recovered from COVID-19); Live viral vaccination within 28 days prior to the first dose of study drug.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kate Chen
Phone
+86 13370266125
Email
kate.chen@bionovapharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Weili Zhao, Prof.
Organizational Affiliation
Shanghai Jiaotong University school of Medicine, Ruijin Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Liling Zhang, Prof.
Organizational Affiliation
Wuhan Union Hospital, China
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jie Jin, Prof.
Organizational Affiliation
The first affiliated hospital, Zhejiang Unviersity school of medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Zhenfang Liu, Prof.
Organizational Affiliation
The First Affiliated School of Guangxi Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Baijun Fang, Prof.
Organizational Affiliation
Henan Oncology Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Zhengming Jin, Prof.
Organizational Affiliation
The First Affiliated Hospital of Soochow University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The first affiliated hospital, Zhejiang Unviersity school of medicine
City
Hangzhou
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jie Jin
Facility Name
The First Affiliated School of Guangxi Medical University
City
Nanning
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhenfang Liu, Prof.
First Name & Middle Initial & Last Name & Degree
Zhenfang Liu, Prof.
Facility Name
Shanghai Jiao Tong University School of Medicine, Ruijin Hospital
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weili Zhao, Prof.
First Name & Middle Initial & Last Name & Degree
Weili Zhao, Prof.
Facility Name
The First Affiliated Hospital of Soochow University
City
Suzhou
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhengming Jin, Prof.
First Name & Middle Initial & Last Name & Degree
Zhengming Jin, Prof.
Facility Name
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
City
Wuhan
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liling Zhang, Prof.
First Name & Middle Initial & Last Name & Degree
Liling Zhang, Prof.
Facility Name
Henan Oncology Hospital
City
Zhengzhou
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Baijun Fang, Prof.
First Name & Middle Initial & Last Name & Degree
Baijun Fang, Prof.

12. IPD Sharing Statement

Learn more about this trial

Study of BN301, an Anti-CD74 Antibody Drug Conjugate, in Patients With Advanced B-Cell Malignancies

We'll reach out to this number within 24 hrs